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Studies have found that matrix metalloproteinase-9 (MMP-9) plays a significant role in cancer cell invasion, metastasis, and tumor growth. But it is a challenge to go for highly sensitive and selective detection and targeting of MMP-9 due to the similar structure and function of the MMP proteins family. Herein, a novel surface-enhanced Raman scattering (SERS) sensing strategy was developed based on the aptamer-induced SERS "hot spot" formation for the extremely sensitive and selective determination of MMP-9. To develop the nanosensor, one group of gold nanospheres was modified with MMP-9 aptamer and its complementary strand DNA1, while DNA2 (complementary to DNA1) and the probe molecule 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) were grafted on the surface of the other group of gold nanospheres. In the absence of MMP-9, DTNB located on the 13-nm gold nanospheres has only generated a very weak SERS signal. However, when MMP-9 is present, the aptamer preferentially binds to the MMP-9 to construct MMP-9–aptamer complex. The bare DNA1 can recognize and bind to DNA2, which causes them to move in close proximity and create a SERS hot spot effect. Due to this action, the SERS signal of DTNB located at the nanoparticle gap is greatly enhanced, achieving highly sensitive detection of MMP-9. Since the hot spot effect is caused by the aptamer that specifically recognizes MMP-9, the approach exhibits excellent selectivity for MMP-9 detection. Based on the benefits of both high sensitivity and excellent selectivity, this method was used to distinguish the difference in MMP-9 levels between normal and cancer cells as well as the expression of MMP-9 from cancer cells with different degrees of metastasis. In addition, this strategy can accurately reflect the dynamic changes in intracellular MMP-9 levels, stimulated by the MMP-9 activator and inhibitor. This strategy is expected to be transformed into a new technique for diagnosis of specific cancers related to MMP-9 and assessing the extent of cancer occurrence, development and metastasis. [ABSTRACT FROM AUTHOR]

Volatile organic compounds detection technology, electronic nose, is promising in various applications such as health management, environmental monitoring, public safety, agriculture, and food production. The critical point of electronic nose to achieve good recognition ability, the fundament for applications, is the generation of high-quality signal characteristics that are transduced from each sensor unit, and aided with algorithm. However, chamber without uniform fluidic state introduce sensors' locations caused artificial characteristics to make the recognition difficult, even incredible. Inspired by the structure of the nasal cavity, a small volume chamber with well-controlled fluidic behavior is designed and fabricated according to theoretical simulation. All the expected fluidic features, including uniform flow field and concentration field, are achieved, which are experimentally demonstrated by humidity and 2-hexanone detection using sensors arrays. The well controlled fluidic behaviors of volatile analytes help achieving the ultra-sensitive volatile organic compounds detection, which might shed a new light for e-nose technology to go over the gap between academics and industry. [ABSTRACT FROM AUTHOR]

Complexity and difficulties in wound management are pressing concerns that affect patients' quality of life and may result in tissue infection, necrosis, and loss of local and systemic functions. Hence, novel approaches to accelerate wound healing are being actively explored over the last decade. Exosomes as important mediators of intercellular communications are promising natural nanocarriers due to their biocompatibility, low immunogenicity, drug loading and targeting capacities, and innate stability. More importantly, exosomes are developed as a versatile pharmaceutical engineering platform for wound repair. This review provides an overview of the biological and physiological functions of exosomes derived from a variety of biological origins during wound healing phases, strategies for exosomal engineering, and therapeutic applications in skin regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

Macrophages are essential immune cells and play a major role in the immune response as pro-inflammatory or anti-inflammatory agents depending on their plasticity and functions. Infiltration and activation of macrophages are usually involved in wound healing. Herein, we first described macrophage polarization and their critical functions in wound healing process. It is addressed how macrophages collaborate with other immune cells in the wound microenvironment. Targeting macrophages by manipulating or re-educating macrophages in inflammation using nanomedicines is a novel and feasible strategy for wound management. We discussed the design and physicochemical properties of nanomaterials and their functions for macrophages activation and anti-inflammatory signaling during wound therapy. The mechanism of action of the strategies and appropriate examples are also summarized to highlight the pros and cons of those approaches. Finally, the potential of nanomedicines to modulate macrophage polarization for skin regeneration is discussed. [ABSTRACT FROM AUTHOR]

To overcome the challenges of poor wound diagnosis and limited clinical efficacy of current wound management, wound dressing materials with the aim of monitoring various biomarkers vital to the wound healing process such as temperature, pH, glucose concentration, and reactive oxygen species (ROS) and improving the therapeutic outcomes have been developed. These innovative theranostic dressings are smartly engineered using stimuli-responsive biomaterials to monitor and regulate local microenvironments and deliver cargos to the wound sites in a timely and effective manner. This review provides an overview of recent advances in novel theranostics for wound monitoring and therapy as well as giving insights into the future treatment of wounds via smart design of theranostic materials. [Display omitted] • This review discusses the management of wound healing and relevant strategies for improved skin regeneration. • This review describes point-of-care wound monitoring systems response to the stimulus of the pH, temperature, glucose concentration, ROS, etc. • This review provides a systematic summary of multifunctional wound theranostic materials and their therapeutic effects for the promotion of wound healing. • This review offers a prospective on application of stimuli responsive theranostic materials and the development of smart wound dressing materials. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is a non-invasive imaging technology that can reveal molecular alterations in the brains of Alzheimer's disease (AD) patients with high sensitivity and specificity, which is crucial for clinical diagnosis, disease staging, and monitoring potential therapeutic approaches. Several biomarkers contribute to the clinical diagnosis of AD, and according to the evolving ATX(N) framework, these biomarkers can be classified into the amyloid- β (A) pathway, Tau-mediated pathophysiology (T), neurodegeneration (N), and other related molecular and cellular network changes in the AD continuum (X), such as neuroinflammation, synaptic dysfunction, and neurochemical deficits. This review provides an overview of PET tracers reported for several typical and classical targets in early AD diagnosis and compares tracers targeting the same biomarkers. We believe this review will support and facilitate progress in early AD diagnosis and further propose the future potential of both PET tracers and targets. [Display omitted] • Biomarkers of the ATX(N) framework are significant in guiding the diagnosis of AD. • PET imaging can non-invasively visualize changes in various AD biomarkers. • Specific PET tracers of these AD biomarkers are well-summarized. [ABSTRACT FROM AUTHOR]

Case-1 and case-2 interval-censored failure time data commonly occur in medical research as well as other fields and many methods have been developed for their analysis under different frameworks. In this paper, we consider regression analysis of such data and present a general class of nonparametric transformation models. One major advantage of these models is their flexibility and generality as they include the linear transformation model as a special case. For estimation of regression parameters, we propose a weighted rank (WR) estimation procedure and establish the consistency and asymptotic normality of the resulting estimator. Furthermore, to estimate the asymptotic covariance matrix of the proposed estimator, a resampling technique, which does not involve nonparametric density estimation or numerical derivatives, is developed. A numerical study is also conducted and suggests that the proposed methodology works well in practice. Finally an application is provided. [ABSTRACT FROM AUTHOR]

We propose adaptive empirical likelihood (EL) estimators to improve estimation efficiency of existing adaptive estimators of the mean response with non-ignorable non-response data. The proposed adaptive EL estimators achieve semiparametric efficiency if the missing probability and conditional distribution of outcome given covariates among the complete cases are both correctly specified. Moreover, if the missing probability is specified correctly, the proposed estimator still achieves a semiparametric efficiency lower bound within a more general class of estimating functions, even if the conditional distribution of outcome is misspecified. The adaptive EL ratio statistic can be used to test whether the missing of the responses is non-ignorable or at random. We also propose kernel-assisted EL estimators of the mean response which achieve semiparametric efficiency if missing probability is correctly specified. The theoretical results are confirmed by a simulation study. A real data example is used to illustrate the proposed adaptive EL method. [ABSTRACT FROM AUTHOR]

Graphical abstract Metal-organic framework derived porous ternary ZnCo 2 O 4 nanoplate arrays grown on carbon cloth have been synthesized, which exhibit excellent performance as binder-free electrodes for lithium-ion batteries. Highlights • Porous ternary ZnCo 2 O 4 nanoplate arrays (NPAs) grown on carbon cloth are synthesized. • The porous ternary ZnCo 2 O 4 NPAs are derived from metal-organic frameworks. • The ZnCo 2 O 4 NPAs exhibit excellent performance as binder-free electrodes for lithium-ion batteries. Abstract Metal-organic frameworks (MOFs) derived ternary transition metal oxide nanostructures have attracted considerable attention for their important applications in energy-related fields. However, most of the present reports on MOFs-derived materials are in the powder form, which should be further mixed with polymer binder and conductive agents before they are coated on current conductor. In this work, we demonstrate a facile solution method to grow the bimetallic zinc/cobalt zeolitic imidazolate frameworks nanoplate arrays (Zn/Co-ZIF NPAs) on carbon cloth (CC) substrate and then they are well converted to porous ternary ZnCo 2 O 4 NPAs on CC after an annealing treatment in air. When investigated as binder-free electrodes for lithium-ion batteries (LIBs), the ZnCo 2 O 4 NPAs/CC electrode exhibits a high area capacity of 3.01 mA h cm−2 (corresponding to 1341.7 mA h g−1 for the ZnCo 2 O 4 NPAs) at the current density of 0.24 mA cm−2 for 100 cycles, which is much higher than that of the Co 3 O 4 NPAs/CC electrode (1.93 mA h cm−2). Moreover, at a high current density of 1.20 mA cm−2, the ZnCo 2 O 4 NPAs/CC electrode can still maintain a high capacity of 2.05 mA h cm−2. The excellent electrochemical performance could be attributed to the unique morphology, structure and composition of the porous ternary ZnCo 2 O 4 NPAs, as well as directly grown on current collector. [ABSTRACT FROM AUTHOR]

Construction bimetallic transition metal selenides with complex hollow structures is of significant importance but also extremely challenging. In this work, starting form metal-organic frameworks (MOFs), we have successfully synthesized the unique hierarchical (Ni 0.33 Co 0.67 )Se 2 complex hollow spheres (CHSs), which manifest high specific capacitance as well as excellent rate performance and cycling stability, making them promising electrode materials for pseudocapacitors. The hierarchical (Ni 0.33 Co 0.67 )Se 2 CHSs display a high specific capacitance of 827.9 F g −1  at the current density of 1 A g −1 and can still retain 646.2 F g −1  at a very high current density of 30 A g −1 . Besides, a high capacitance of 865.8 F g −1 is obtained after cycling at 6 A g −1 for 2000 cycles, indicating good cycling stability. The excellent electrochemical performance could be owing to their high electrical conductivity and hierarchical complex hollow structure. Furthermore, an asymmetric supercapacitor (ASC) device employing (Ni 0.33 Co 0.67 )Se 2 CHSs as positive electrode and activated carbon (AC) as negative electrode is also fabricated, which displays a high energy density of 29.1 Wh kg −1  at a power density of 800 W kg −1 . These electrochemical results indicate the hierarchical (Ni 0.33 Co 0.67 )Se 2 CHSs could be promising electrode materials for pseudocapacitors. The present work might also contribute to the rational construction of metal selenides with complex hollow structures for high-performance energy storage. [ABSTRACT FROM AUTHOR]

Caspase-3 is an important biomarker for the process of apoptosis, which is a key target for cancer treatment. Due to its low concentration in single cells and the structural similarity of caspase family proteins, it is exceedingly challenging to accurately determine the intracellular caspase-3 during apoptosis in situ. Herein, a biosensing strategy based on the target-induced SERS "hot spot" formation has been developed for the simultaneous highly sensitive and selective detection of intracellular caspase-3 level. The nanosensor is composed of gold nanoparticles modified with the probe molecule 4-mercaptophenylboronic acid (4-MPBA) and a peptide chain. The well-designed peptide chain contains two distinct functional domains, one with a sulfhydryl group for bonding to the gold nanoparticles and the other a fragment specifically recognized by caspase-3. When caspase-3 is present, the negatively charged segment (NH2–Asp–Asp–Asp–Glu–Val–Asp–OH) of the peptide chain is specifically hydrolyzed, leaving a positively charged fragment coated on the surface of the gold nanoparticles. At this time, the golden nanoparticles undergo significant coupling aggregation due to the electrostatic interaction, resulting in a large number of SERS "hot spot" formation. The SERS signal of the 4-MPBA located at the nano-gap is significantly boosted because of the local plasma enhancement effect. The highly sensitive determination of caspase-3 can be achieved according to the altered SERS signal intensity of 4-MPBA. The turn-on of the SERS signal-induced target contributes to the excellent selectivity and the formation of the SERS "hot spot" effect that further improves the sensitivity of caspase-3 detection. The advantages of this biosensing technique allow for the precise in situ monitoring of the dynamic changes in caspase-3 levels during apoptosis. In addition, the differences in caspase-3 levels during the apoptosis of various cell types were compared. Monitoring the caspase-3 levels can be used to track the cellular apoptosis process, evaluate the effect of drugs on cancer cells in real time, and provide guidance for the selection of the appropriate drug dosage. [ABSTRACT FROM AUTHOR]

Ferroptosis is a non-apoptotic cell death regulated by iron-dependent lipid peroxidation. Glutathione (GSH), a key antioxidant against oxidative damage, is involved in one of the most important metabolic pathways of ferroptosis. Herein, an excellent plasmonic nanoprobe was developed for highly sensitive, in situ, dynamic real-time monitoring of intracellular GSH levels during ferroptosis. A nanoprobe was prepared by functionalizing gold nanoparticles (AuNPs) with the probe molecule crystal violet (CV). The fluctuation in the SERS signal intensity of CV via the competitive displacement reaction can be used to detect GSH. The advantages of the plasmonic nanoprobe including low-cost production techniques, outstanding stability and biocompatibility, high specificity and sensitivity towards GSH with a detection limit of 0.05 μM. It enables real-time dynamic monitoring of GSH levels in living cells during erastin-induced ferroptosis. This approach is expected to provide important theoretical support for elucidating the GSH-related ferroptosis metabolic mechanism and advancing our understanding of ferroptosis-based cancer therapy. [ABSTRACT FROM AUTHOR]

For various neurodegenerative diseases, including Alzheimer's disease (AD), the abnormal aggregation of Tau is not only the predominant contributing factor but also a major biomarker for disease diagnosis. In this study, a series of aza-fused tricyclic derivatives were designed and synthesized. By changing the position and number of nitrogen atoms on the fused tricyclic core, the imidazonaphthyridine scaffold was screened and reported for the first time which could potentially detect Tau aggregates. Through a series of in vitro and in vivo biological evaluations, probe [125I] 5 possessed exceptional binding affinity (IC 50 = 1.63 nM) to neurofibrillary tangles in the AD brain, high selectivity over Aβ plaques (23.4-fold), clean off-target profile to monoamine oxidase A/B (MAO-A/B), and suitable pharmacokinetics (initial brain uptake = 3.22% ID/g). [Display omitted] • Aza-fused tricyclic derivatives were discovered as Tau binding scaffold. • [125I] 5 possessed high binding affinity to Tau, high selectivity for Aβ plaques. • [125I] 5 displayed clean off-target profile to monoamine oxidase A/B. • [125I] 5 displayed suitable pharmacokinetics in mice. [ABSTRACT FROM AUTHOR]

The micro-structural characteristics of sodium dodecyl sulfate (SDS)/benzyl alcohol (BA)/HO micelle were studied by the methods of theoretical calculation, viscosity, dynamic light scattering, and Raman spectra. The radius of the spherical micelle was about 22.86-35.85 nm. The maximum length of rod-like micelle could reach up to 250.95 nm. In the micelle, the carbon chain of SDS was not completely stretched but still bended. The total chain length of SDS molecule in the micelle appeared to be 2 nm approximately. Both the axis ratio and the shape factor of rod-like micelles increased with the increase of aggregation number. The intrinsic viscosity and relative viscosity of spherical micelles were less than those of the rod-like micelles. The relative viscosity and critical micelle concentration values decreased gradually with the increase of BA content. The second critical micelle concentration of surfactant could also be determined through viscosity method. [ABSTRACT FROM AUTHOR]

This paper proposes an empirical likelihood-based weighted (ELW) quantile regression approach for estimating the conditional quantiles when some covariates are missing at random. The proposed ELW estimator is computationally simple and achieves semiparametric efficiency if the probability of missingness is correctly specified. The limiting covariance matrix of the ELW estimator can be estimated by a resampling technique, which does not involve nonparametric density estimation or numerical derivatives. Simulation results show that the ELW method works remarkably well in finite samples. A real data example is used to illustrate the proposed ELW method. [ABSTRACT FROM AUTHOR]

Hollow fiber membrane (HFM) culture system is one of the most important bioreactors for the large-scale culture and expansion of therapeutic cells. However, enzymatic and mechanical treatments are traditionally applied to harvest the expanded cells from HFMs, which inevitably causes harm to the cells. In this study, thermo-responsive cellulose acetate HFMs for cell culture and non-invasive harvest were prepared for the first time via free radical polymerization in the presence of cerium (IV). ATR-FTIR and elemental analysis results indicated that the poly(N-isopropylacrylamide) (PNIPAAm) was covalently grafted on HFMs successfully. Dynamic contact angle measurements at different temperatures revealed that the magnitude of volume phase transition was decreased with increasing grafted amount of PNIPAAm. And the amount of serum protein adsorbed on HFMs surface also displayed the same pattern. Meanwhile osteoblasts adhered and spread well on the surface of PNIPAAm-grafted HFMs at 37 °C. And Calcein-AM/PI staining, AB assay, ALP activity and OCN protein expression level all showed that PNIPAAm-grafted HFMs had good cell compatibility. After incubation at 20 °C for 120 min, the adhering cells on PNIPAAm-grafted HFMs turned to be round and detached after being gently pipetted. These results suggest that thermo-responsive HFMs are attractive cell culture substrates which enable cell culture, expansion and the recovery without proteolytic enzyme treatment for the application in tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

Highlights: [•] The microcapsules as gel breakers were prepared by in situ polymerization. [•] The microcapsules were composed of ammonium persulfate core and polypyrrole shell. [•] The release time of ammonium persulfate from the microcapsules was controllable. [•] The prepared microcapsules had good storage stability at room temperature. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two plasma proteins were adsorbed on three typical TiO 2 nanostructures. • Surface topographies of nanostructures can be affected by protein adsorption. • Bactericidal performance of nanostructures is weakened due to the changes in geometric dimensions after BSA adsorption. • Bactericidal efficiency of nanostructures against E. coli can be significantly improved due to the presence of HFN layer on the top of the nanostructures, which may cause higher stress of nanocones to cell membrane. Bionic nanostructures have broad potential applications for achieving the surface mechano-bactericidal performance especially for titanium extensively used as implants. However, the surface topographies of these nanostructures may be changed by protein adsorption in vivo, which possibly affects the sterilization of nanostructures. Herein, two plasma proteins, bovine serum albumin (BSA) and human serum fibronectin (HFN), were adsorbed onto three typical TiO 2 nanostructures respectively, and the topographies as well as the subsequent bacterial behavior of Escherichia coli and Staphylococcus aureus were investigated. The results show that after BSA adsorption, the height of the nanostructures is reduced and the radius of the nanocones is increased for three typical nanostructures, weakening the surface bactericidal performance. Whereas, after HFN adsorption, the proteins are adsorbed at different positions of nanostructures, affecting their bactericidal efficiency. Notably, the bactericidal efficiency of nanowire clusters and nanowire/sheet clusters against Escherichia coli is significantly improved from ∼ 49.64% and ∼ 83.25% to ∼ 64.89% and ∼ 93.67% due to the presence of HFN layer on the top of the nanostructures, which may cause higher stress to cell membrane by nanocones. Our results demonstrate that the bactericidal performance of implant is impacted by the combined effect of surface nanostructure and protein layer. [ABSTRACT FROM AUTHOR]

Abstract: Multicellular tumour spheroids closely recapitulate the physiological environment of tumour tissues. However, their implementation in drug screening assays remains limited due to the technological challenges of forming large numbers of high quality spheroids in platforms compatible with high throughput screening. A simple bench-top microfabrication strategy is demonstrated here based on the principle of ice lithography carried out on superhydrophobic substrates to fabricate quasi-spherical microwells (spheriwells). The microwells shapes and dimensions are directly controlled by the hydrophobicity of the substrate and the volume of the water droplets. The prepared concave microwells enable the formation of dense and homogeneous multicellular tumour spheroids. Spheroids formed within spheriwells are trapped within the microwells, which eliminate loss during media manipulation and facilitate long-term on-chip culture. Morphological and phenotypical changes associated with the growth of MCF-7 adenocarcinoma cells in spheriwells were characterised using imaging flow cytometry and revealed the appearance of heterogeneous populations with loss of E-Cadherin expression. The compatibility of the spheriwells with an on-chip MTT assay is demonstrated. The very unusual shape of the spheriwells, prepared using materials and methods routinely used in most research laboratories, provides a straightforward and scalable platform to prepare high quality multicellular tumour spheroids compatible with high throughput biological screening assays. [Copyright &y& Elsevier]

The method of generalized estimating equations (GEE) introduced by K. Y. Liang and S. L. Zeger has been widely used to analyze longitudinal data. Recently, this method has been criticized for a failure to protect against misspecification of working correlation models, which in some cases leads to loss of efficiency or infeasibility of solutions. In this paper, we present a new method named as 'weighted estimating equations (WEE)' for estimating the correlation parameters. The new estimates of correlation parameters are obtained as the solutions of these weighted estimating equations. For some commonly assumed correlation structures, we show that there exists a unique feasible solution to these weighted estimating equations regardless the correlation structure is correctly specified or not. The new feasible estimates of correlation parameters are consistent when the working correlation structure is correctly specified. Simulation results suggest that the new method works well in finite samples. [ABSTRACT FROM AUTHOR]

Highlights: [•] We constructed polycistronic plasmid carrying four reprogramming factor (OSKM). [•] Human adipose mesenchymal stem cells were reprogrammed into iPS cells. [•] ADSCs derived iPS cells switch to neural differentiation after induction. [•] Neural differentiated cells had normal karyotypes and no insertion mutation. [•] The method provides potential strategy for patient-specific neural cells therapy. [ABSTRACT FROM AUTHOR]

Abstract: In clinical and epidemiological studies, matched case-control designs have been used extensively to investigate the relationships between disease/response and exposure/covariate. Due to the retrospective nature of the study, some covariates may not be observed for all study subjects and missing covariate information may create bias and reduce the efficiency of the parameter estimates. We explore the use of profile empirical likelihood (EL) to cope with this situation by combining unbiased estimating equations when the number of estimating equations is greater than the number of unknown parameters. For high dimensional covariates, we propose a weighted conditional likelihood (WCL) method to solve the computational problem of the profile EL method. The proposed EL and WCL methods can achieve semiparametric efficiency if the probability of missingness is correctly specified. Based on the EL and WCL functions, we also develop Wilks’ type tests and corresponding confidence regions for the model parameters. A simulation study is conducted to assess the performance of the proposed methods in terms of robustness and efficiency. [Copyright &y& Elsevier]

The effect of solubilization-hydrotrope action of vitamin C (Vc) on the corrosion behavior of nickel is studied by electrochemical and SEM methods in a CTAB/n-C5Hl1OH/Vc/H2O micelle system. With the increase of Vc content, the solubilization-hydrotrope action and the corrosion rates of nickel increase. But the pure resistance of the system and the differential capacitance on nickel surface decrease. The effect in the CTAB/n-C5Hl1OH/HCl/H2O system is less than that in the CTAB/n-C5Hl1OH/H2O system. [ABSTRACT FROM AUTHOR]

Abstract: This study was designed to demonstrate the potential of small nanoparticulate lymphotropic contrast agents designed to bind with high affinity to lymphoid cells overexpressing the CD45 antigen. To this end, small gold nanoparticles used as model were conjugated to anti-CD45 antibodies and injected in mice in the dorsal toe of the fore/hind paw. Chemical analysis demonstrated rapid uptake and transport of the nanoparticles in the lymphatic as well as significant retention of the nanoparticles with high binding affinity to lymphoid cells in the popliteal and axillary lymph nodes in comparison to non-targeted nanoparticles. [Copyright &y& Elsevier]

Gold nanoparticles are of high interest in the biodiagnosticandbioimaging field owing to their unique optical properties such aslocalized surface plasmon resonance (LSPR) and high Rayleigh scatteringefficiency in the visible range. Although biofunctionalization isa prerequirement prior to their integration in diagnostic procedures,aggregation-free conjugation of biomacromolecules to large gold nanoparticleis not trivial. Here, a robust and simple method based on commerciallyavailable reactants is reported for the efficient biofunctionalizationof gold nanoparticles with sizes ranging from 15 to 175 nm. It isdemonstrated that mixed poly(ethylene glycol) (PEG) layers, preparedusing specific ratios of low- and high-molecular-weight PEG chains,can be conjugated to proteins and monoclonal antibodies using standardcarbodiimide chemistry without detectable aggregation. The propertiesof the mixed PEG interlayer modified gold nanoparticles were investigatedusing UV–vis spectrometer, dynamic light scattering, and X-rayphotoelectron spectroscopy, which demonstrated the importance of controllingbiointerfacial properties. Using the epithelial cell adhesion molecule(EpCAM) as a model target antigen, the benefit of the mixed PEG layersover coatings prepared using high-molecular-weight PEG chains onlyis demonstrated in vitro using bright field microscopy and reflectanceconfocal microscopy. Very high binding affinity to breast cancer cellswas obtained for the mixed PEG layers. This robust procedure demonstratesthat, under optimal conditions, a compromise can be achieved betweenthe excellent steric protection provided by thick PEG adlayers andthe high bioconjugation yields afforded by adlayers from low-molecular-weighttethers. [ABSTRACT FROM AUTHOR]

Abstract: By only specifying the conditional mean and variance functions of the response variable given covariates, the quasi-likelihood can produce valid semiparametric inference for regression parameter in generalized linear models (GLMs). However, in many studies, auxiliary information is available as moment restrictions of the marginal distribution of the response variable and covariates. We propose the combined quasi and empirical likelihood (CQEL) to incorporate such auxiliary information to improve the efficiency of parameter estimation of the quasi-likelihood in GLMs with missing responses. We show that, when assuming responses are missing at random (MAR), the CQEL estimator achieves better efficiency than the maximum quasi-likelihood (MQL) estimator due to utilization of the auxiliary information. When there is no auxiliary information, we show that the CQEL estimator of the mean response is more efficient than the existing imputation estimators. Based on the asymptotic property of the CQEL estimator, we also develop Wilks’ type tests and corresponding confidence regions for the regression parameter and mean response. The merits of the CQEL are further illustrated through simulation studies. [Copyright &y& Elsevier]

Abstract: We propose a nonparametric method, called rank-based empirical likelihood (REL), for making inferences on medians and cumulative distribution functions (CDFs) of k populations. The standard distribution-free approach to testing the equality of k medians requires that the k population distributions have the same shape. Our REL-ratio (RELR) test for this problem requires fewer assumptions and can effectively use the symmetry information when the distributions are symmetric. Furthermore, our RELR statistic does not require estimation of variance, and achieves asymptotic pivotalness implicitly. When the k populations have equal medians we show that the REL method produces valid inferences for the common median and CDFs of k populations. Simulation results show that the REL approach works remarkably well in finite samples. A real data example is used to illustrate the proposed REL method. [Copyright &y& Elsevier]

Observations on continuous populations are often rounded when recorded due to the precision of the recording mechanism. However, classical statistical approaches have ignored the effect caused by the rounding errors. When the observations are independent and identically distributed, the exact maximum likelihood estimation (MLE) can be employed. However, if rounded data are from a dependent structure, the MLE of the parameters is difficult to calculate since the integral involved in the likelihood equation is intractable. This paper presents and examines a new approach to the parameter estimation, named as 'short, overlapping series' (SOS), to deal with the α-mixing models in presence of rounding errors. We will establish the asymptotic properties of the SOS estimators when the innovations are normally distributed. Comparisons of this new approach with other existing techniques in the literature are also made by simulation with samples of moderate sizes. [ABSTRACT FROM AUTHOR]

Abstract: Many statistical models, e.g. regression models, can be viewed as conditional moment restrictions when distributional assumptions on the error term are not assumed. For such models, several estimators that achieve the semiparametric efficiency bound have been proposed. However, in many studies, auxiliary information is available as unconditional moment restrictions. Meanwhile, we also consider the presence of missing responses. We propose the combined empirical likelihood (CEL) estimator to incorporate such auxiliary information to improve the estimation efficiency of the conditional moment restriction models. We show that, when assuming responses are strongly ignorable missing at random, the CEL estimator achieves better efficiency than the previous estimators due to utilization of the auxiliary information. Based on the asymptotic property of the CEL estimator, we also develop Wilks’ type tests and corresponding confidence regions for the model parameter and the mean response. Since kernel smoothing is used, the CEL method may have difficulty for problems with high dimensional covariates. In such situations, we propose an instrumental variable-based empirical likelihood (IVEL) method to handle this problem. The merit of the CEL and IVEL are further illustrated through simulation studies. [ABSTRACT FROM AUTHOR]

Vesicles have been prepared at a constant molar ratio of L-glutamic acid/1-aminodecane/ibuprofen/H2O. The fusion dynamics of the vesicles have been directly observed and followed by using optical microscopy and freeze fracture replication-electron microscopy technologies. With time increasing up to 25 minutes, the vesicles slowly fuse to form large stable vesicles. A membrane phase transition temperature is detected at 97°C. [ABSTRACT FROM AUTHOR]

The expansion of umbilical cord blood mononuclear cells (UCB MNCs) was investigated in a novel co-culture system by means of encapsulation of rabbit bone marrow (BM) mesenchymal stem cells (MSCs) in alginate beads (Alg beads). Three kinds of media were applied and the experiments lasted for 7 days. The total nucleated cell density was measured every 24 h. Flow cytometric assay for CD34+ cells and methylcellulose colony assays were carried out at 0, 72 and 168 h. It was found that the encapsulated MSCs illustrated remarkable effects on UCB MNCs expansion regardless of whether serum is present in culture media or not. At the end of 168 h co-culture, the total nucleated cell number was multiplied by 15 ± 2.9 times, and CD34+ cells 5.3 ± 0.3 times and colony-forming units in culture (CFU-Cs) 5.6 ± 1.2 times in the serum-free media supplemented with conventional dose of cytokines, which was very similar to the results in the containing 20% serum media. While in the control, i.e. MNC expansion without encapsulated MSCs, however, total nucleated cells density changed mildly, CD34+ cells and CFU-Cs showed little effective expansion. It is demonstrated that the encapsulated stromal cells can support the expansion of UCB MNCs effectively under the experimental condition. [ABSTRACT FROM AUTHOR]

Abstract: The critical micelle concentration of aminodecane-glutamic acid (bio-active substance, C10G) is 1.6×10−2 molL−1 using surface tension and conductivity measurements. The additions of ibuprofen, glucose and salt lead to the decrease of the critical micelle concentration. The nanospheres with a radius of 40–80nm can be prepared in C10G/ibuprofen/H2O system. The stability of the nanospheres is about 180 days. Glucose, pH and NaCl all have the effects on the size and dispersion behaviors of the nanospheres. [Copyright &y& Elsevier]

[Display omitted] • 3D thin wall with turgor pressure finite element model of bacterial cell was build. • The AFM indentation experiments of E. coli cell were simulated using 3D-TWTP-FEM. • Investigation of mechano-bactericidal mechanism of nanostructured surfaces. • This study reveals the maximum stress location of the cells adhered to nanopillars. • Optimal nanopillar geometry for mechanically killing bacteria. The mechano-bactericidal property of nanostructured surfaces has become the focus of intensive research toward the development of a new generation of antibacterial surfaces, especially in the current era of spreading antibiotic resistance. However, the mechanisms underlying nanostructured surfaces mechanically damaging bacteria remain unclear, which ultimately limits translational potential toward real-world applications. Using finite element simulation technique, we developed the three-dimensional thin wall with turgor pressure finite element model (3D-TWTP-FEM) of bacterial cell and verified the reliability of this model by the AFM indentation experiment simulation of the cell, and the cell model is able to simulate suspended bacterial cell and the process of cell adhering to the flat and nanopillar surfaces. Since bacterial cells suffer greater stress and deformation on the nanopillar surfaces, a two-stage model of the elastic and creep deformation stage of the cells on the nanostructured surfaces was developed. The calculations show that the location of the maximum stress/strain on the cells adhered to the nanopillar surfaces is at the liquid-cell-nanopillar three phase contact line. The computational results confirmed the ability of nanostructured surfaces to mechanically lyse bacteria and gave the effect of nanopillar geometry on the efficiency and speed of bacterial cell rupture. This study provides fundamental physical insights into how nanopillar surfaces can serve as effective and fast mechanical antimicrobial materials. [ABSTRACT FROM AUTHOR]

To further study the proliferation and multi-differentiation potentials of adipose-derived stem cells (ADSCs), the cells were isolated with improved methods and their growth curves were achieved with cck-8. Surface protein expression was analyzed by flow cytometry to characterize the cell phenotype. The multi-lineage potential of ADSCs was testified by differentiating cells with adipogenic, chondrogenic, osteogenic, and myogenic inducers. The results showed that about 5 × 105 stem cells could be obtained from 400 to 600 mg adipose tissue. The ADSCs can be continuously cultured in vitro for up to 1 month without passage and they have several logarithmic growth phases during the culture period. Also, the flow cytometry analysis showed that ADSCs expressed high levels of stem cell-related antigens (CD13, CD29, CD44, CD105, and CD166), while did not express hematopoiesis-related antigens CD34 and CD45, and human leukocyte antigen HLA-DR was also negative. Moreover, stem cell-related transcription factors, Nanog, Oct-4, Sox-2, and Rex-1 were positively expressed in ADSCs. The expression of alkaline phosphatase (ALP) was detected in the early osteogenic induction and the calcified nodules were observed by von Kossa staining. Intracellular lipid droplets could be observed by Oil Red staining. Differentiated cardiomyocytes were observed by connexin43 fluorescent staining. In order to obtain more stem cells, we can subculture ADSCs every 14 days instead of the normal 5 days. ADSCs still keep strong proliferation ability, maintain their phenotypes, and have stronger multi-differentiation potential after 25 passages. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Stable vesicles and microspheres are directly prepared in amino acid/dodecylamine (DA)/ibuprofen/H2O system. Vesicle can be automatically formed in glycine/DA/H2O system. No vesicle and microsphere are found in l-glutamic acid or l-histidine/DA/H2O systems. When ibuprofen is added into amino acid/DA/H2O system, vesicles and microspheres can be formed and coexisted. Ibuprofen can regulate the quantity ratios between the vesicles and the microspheres. The structure properties of amino acid affect on the stabilities of the vesicles and microspheres. The formation mechanisms of the vesicles and microspheres are also discussed in this paper. [Copyright &y& Elsevier]

The methods are brought forward to calculate the dimerization equilibrium constant and the mole Gibbs free energy of surfactant in low surfactant concentration according to the forming theories of the organized assembly of surfactant molecule and chemical equilibrium. And a new simple and suitable method is educed to calculate the micelle aggregation equilibrium constant and the mole Gibbs free energy in large-scale surfactant concentration. In SDS/H2O system, the dimerization equilibrium constant Kd=7.6±0.1×103, the mole Gibbs free energy ΔGm,d=-11.07±0.03 kJ · mol-1. In SDS/H2O system and SDS/BA/H2O microemulsion system, the mole Gibbs free energy of spherical micelle ΔGm,s≈-10.88 kJ · mol-1, the mole Gibbs free energy of rod-like micelle ΔGm,r≈-9.80 kJ · mol-1. [ABSTRACT FROM AUTHOR]

Abstract: The highly stable innocuous niosome composed of only three components is successfully prepared in Span 80/PEG 400/H2O system. The niosome properties are studied by some means of freeze fracture replication-transmission electron microscopy, negative staining-transmission electron microscopy, dynamic light scattering and differential scanning calorimetry. The obtained results indicate that the niosome can be stable for over one year. The niosome diameter is between 100 and 180nm. The compositions of the system affect the preparation and properties of the niosome. But the temperature and ionic intensity do not distinctly change the stability and the radius. The formation mechanism of the niosome is discussed in this paper. [Copyright &y& Elsevier]

Abstract: The microstructure and transformation of the niosome prepared from poly(ethylene glycol) (PEG) 6000/Tween 80/Span 80/H2O lamellar liquid crystal (LLC) are studied by the methods of freeze fracture-TEM, negative-staining TEM, dynamic light scattering technique and micropolarity measurements. The size of the niosome made from the LLC is little larger than that from directly mixing samples. The layer membrane of the former niosome is looser than that of the later niosome. The former niosome is held with the partial behaviors of the LLC and can tend to be transformed into the later niosome. [Copyright &y& Elsevier]

Abstract: The structure behaviors of Hemoglobin (Hb) are in detail studied by the methods of UV–vis and fluorescence spectra, circular dichroism, negative staining-TEM, FF-TEM and electrochemistry techniques in PEG 6000/Tween 80/Span 80/H2O niosome system. The obtained results show that Hb can be adsorbed and outspread on the surface of the niosome membrane. The intensities of the UV–vis and fluorescence spectra of Hb in Hb/niosome system are greater than those in Hb/H2O system. The structure behaviors of Hb are partially stabilized and protected in Hb/niosome system. With the increase of PEG 6000 content in the niosome system, the content of α-helix structure decreases but the contents of β-sheet and random increase for Hb. The content of β-turn structure is almost independent of PEG 6000 content. The negative zeta potential of Hb and the conductivity of the system all decrease. The zeta potential of the niosome firstly decreases and then increases. [Copyright &y& Elsevier]

Abstract: Expansion of umbilical cord blood mononuclear cells (UCB MNCs) was carried out in a rotating wall vessel (RWV) bioreactor and tissue culture flasks (T-flasks) in serum-containing medium supplemented with relatively low doses of purified recombinant human cytokines (5.33ng/ml IL-3, 16ng/ml SCF, 3.33ng/ml G-CSF, 2.13ng/ml GM-CSF, 7.47ng/ml FL and 7.47ng/ml TPO) for 8 days. The cell density, pH and osmolality of the culture medium in the two culture systems were measured every 24h. Flow cytometric assay for CD34+ cells was carried out at 0, 144 and 197h and methylcellulose colony assays were performed at 0, 72, 144 and 197h. The pH and osmolality of the medium in the two culture systems were maintained in the proper ranges for hematopoietic stem cells (HSCs) and progenitors culture. The RWV bioreactor, combined with a cell-dilution feeding protocol, was efficient to expand UCB MNCs. At the end of 200h culture, the total cell number was multiplied by 435.5±87.6 times, and CD34+ cells 32.7±15.6 times, and colony-forming units of granulocyte-macrophage (CFU-GM) 21.7±4.9 times. While in T-flasks, however, total cells density changed mildly, CD34+ cells and CFU-GM decreased in number. It is demonstrated that the RWV bioreactor can provide a better environment for UCB MNCs expansion, enhance the contact between HSCs and accessory cells and make the utilization of cytokines more effective than T-flask. [Copyright &y& Elsevier]

Abstract: The nano-Al2O3 and nano-SiO2 particle-modified surfaces were built up by Layer-by-Layer self-assembled method. The properties of these nanoparticle-modified surfaces and the controls were investigated with atomic force microscope for topography analysis. Pseudomonas fluorescens (PF) cell adhesion was evaluated by microscopic determination of the numbers of cells that adhered to the controls and modified surfaces exposed to PF cell suspension under dynamic and static conditions. The results show that the adhesion numbers of PF cells on both surfaces readily increase with the exposition time, and the number on the modified surfaces is much more than that on the controls. Meanwhile, the PF cell morphologies on these nanoparticle-modified surfaces studied by inverted microscope show that the majority of PF cells adhering to the modified surfaces are in presence of clusters, which contributes overwhelming amount to the total adhesion numbers during the later time of cell adhesion; while on the controls, few PF cells are confluent. The results suggest that nanoparticle-modified surfaces may enhance the interactions between bacteria and materials. [Copyright &y& Elsevier]

The forces acting on a microcarrier or a small piece of tissue and its movement in the rotating wall vessel (RWV) bioreactor were analyzed. The tracks of a particle in RWV reactor were calculated under different inner and outer cylinder wall rotating speeds, different particle sizes and different density difference between culture medium and the particle. The results show that cells or particles experience partial microgravity only in the upper area of RWV, which changes with angle θ, while in the lower part of RWV, they experience overweight. The trajectory of a moving particle in RWV reactor is an eccentric helix under ground-based condition. And the eccentric degree increases with the decrease of outer wall rotating speed, and with the increase of density difference and particle size. The proper match of rotating speeds of inner and outer cylinder walls is the key to prevent the particle colliding with the walls. For a relatively large piece of cultivated tissue, it can move around the inner wall only when the rotating speed of the outer cylinder is high. And the drag force acting on a particle inside RWV increases with the particle size and the density difference. [Copyright &y& Elsevier]

A model was developed to evaluate and predict boiling heat transfer enhancement using additives. The model is based on the molecular structures of the additives and uses artificial neural network technology. The effects of 30 additives tested by the authors and other researchers on the augmentation of boiling heat transfer were analyzed with the model. The results show that the evaluation of all 30 additives is consistent with the experimental data, which means that the training accuracy of the model is 100%. In addition, the boiling heat transfer enhancement with sodium oleate and 11 other additives was also predicted, with a prediction accuracy of over 90% since the calculated results for 10 of the 11 additives were in agreement with the experimental results. [Copyright &y& Elsevier]